Insulin Levels In Response Research Articles

Insulin, glucose, and pancreatic polypeptide responses to a test meal in restricting type anorexia nervosa before and after weight restoration

Prolonged malnutrition in individuals with anorexia nervosa (AN) has been associated with alterations in endocrine function that may play a sustaining role in the disorder. We hypothesized that abnormalities in endocrine responses to ingestion of a meal in AN are reversible and depend on weight restoration. We measured meal-induced endocrine responses in AN subjects at three time points during hospitalization: before refeeding (n = 13, mean BMI 16.7 kg/m(2)), after 2 wk of refeeding (mean BMI 18.0 kg/m(2)), and in the weight-restored state (mean BMI 20.3 kg/m(2)). Control subjects (n = 13, BMI 19-24.9 kg/m(2)) were tested once. Tests were 2.5-h sessions in which blood was drawn every 15 min before, during, and after a approximately 650-kcal test breakfast. Relative to controls, peak levels of glucose were depressed and peak levels of insulin in response to ingestion of the test meal were delayed, with response patterns in the third trial most similar to controls. Pancreatic polypeptide (PP) levels were increased in AN relative to controls regardless of weight status. The delay in insulin release and elevated PP levels did not correct with short-term refeeding and may contribute to the high relapse rates and maintenance of AN.

Role of the autonomic nervous system in the development of hyperinsulinemia by high-carbohydrate formula feeding to neonatal rats

An early dietary intervention in the form of a high-carbohydrate (HC) milk formula in neonatal rat pups results in immediate onset of hyperinsulinemia. While increased insulin secretion in HC rats has been shown to be related to hypersensitivity to glucose, the immediate onset of hyperinsulinemia and its persistence throughout the suckling period suggest involvement of multiple systems that enhance insulin secretion in response to increased demand. Evidence presented here in 12-day-old HC rats indicates that altered activity of the autonomic nervous system contributes to enhanced insulin secretory responses to glucose stimulation through increased parasympathetic and decreased sympathetic signaling. Both in vivo and in vitro studies have shown that HC rats secrete significantly higher levels of insulin in response to glucose in the presence of acetylcholine, a cholinergic agonist, while sensitivity to inhibition of insulin secretion by oxymetazoline, an alpha(2a)-adrenergic receptor (alpha(2a)AR) agonist, was reduced. In addition, HC rats showed increased sensitivity to blockade of cholinergic-induced insulin secretion by the muscarinic type 3 receptor (M3R) antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide, as well as increased potentiation of glucose-stimulated insulin secretion by treatment with yohimbine. Increases in islets levels of M3R, phospholipase C-beta1, and protein kinase Calpha mRNAs, as well as decreased alpha(2a)AR mRNA, in 12-day-old HC rats provide a mechanistic connection to the changes in insulin secretion seen in HC rats. In conclusion, altered autonomic regulation of insulin secretion, due to the HC nutritional intervention, contributes to the development of hyperinsulinemia in 12-day-old HC rats.

The HND mouse, a nonobese model of type 2 diabetes mellitus with impaired insulin secretion

This study aimed to develop a novel type 2 diabetes model designated the HND (Horio-Niki diabetic) mouse, by transferring diabetogenic genes from wild castaneus mice (Mus musculus castaneus) captured in the Philippines into laboratory mice (C57BL/6J:B6). Offspring from the cross between a wild male and a B6 female were backcrossed to the sire. One male backcross which exhibited fasting hyperglycemia was crossed with a B6 female to comprise the fundamental stock (F0). Thereafter, full-sib mating was performed, and mice with impaired glucose tolerance were selected and bred from the F2 generation. Characterization of the phenotype of HND mice and insulin release from their islets was evaluated with F12 generation males. The male HND mice were lean, and spontaneously exhibited impaired glucose tolerance at a high incidence rate at 6 weeks of age. Their serum insulin levels in response to intraperitoneal glucose were markedly attenuated. However, glucose-induced insulin release from isolated HND islets was not affected. Notably, inhibition of glucose-induced insulin release by epinephrine was more pronounced in HND islets than in B6 islets. Moreover, in vivo treatment of HND mice with the alpha2-adrenergic receptor agonist clonidine resulted in marked hypoinsulinemic hyperglycemia. We suggest the HND mouse may be a distinctive and useful model for type 2 diabetes with impaired neural control of insulin secretion.

Reduction of adiposity with prolonged growth hormone treatment in old obese rats: effects on glucose handling and early insulin signaling

Objectives Growth Hormone (GH) promotes loss of body fat and causes insulin resistance. It is debated whether reduction of body fat mass during long term growth hormone (GH) administration improves carbohydrate metabolism. To answer this question we assessed carbohydrate handling and tissue specific function of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) during prolonged GH treatment of obese rats. Methods Body fat % estimated by DEXA scanning, plasma IGF-I, glucose and insulin were studied in 17 months old dietary induced obese rats treated for 4, 21 or 41 days (GH: 4 mg/kg/d or saline total n = 90). Adipose tissue, muscle and liver samples were obtained after 21 days and expression and tyrosine phosphorylation of IR and IRS-1 proteins and the degree of IRS-1-Janus Kinase-2 (JAK2) interaction were analyzed by immunoprecipitation and immunoblotting. Results Forty-one days GH treatment caused the body fat to decline significantly to 20 ± 3% (Mean ± SEM), whereas it remained steady on 51 ± 4% in the pair fed group. Insulin levels in response to OGTT were significantly elevated throughout the experiment. IR amount was elevated in adipose tissue but decreased in liver after GH treatment while IR phosphorylation was increased in muscle only. IRS-1 amount was elevated in adipose tissue and muscle while IRS-1 phosphorylation was increased only in liver. The association of IRS-1 with JAK-2 was increased in liver and muscle. Conclusions An extensive reduction of fat mass did not improved signs of insulin resistance in GH treated old obese rats. The molecular events associated with GH treatment included tissue specific changes in the function of IR and IRS-1 suggesting the liver to be the primary site of insulin resistance. Furthermore, the association of IRS-1with JAK-2 in the course of GH signaling could present a mechanism for GH to directly induce insulin resistance.

Preserved glucoregulation but attenuation of the vascular actions of insulin in mice heterozygous for knockout of the insulin receptor.

Type 2 diabetes is preceded by years of insulin resistance and is characterized by reduced bioavailability of the antiatherosclerotic signaling molecule nitric oxide (NO) and premature atherosclerosis. The relationship between resistance to the glucoregulatory actions of insulin and its effects on the vasculature (in particular NO-dependent responses) is poorly characterized. We studied this relationship in mice heterozygous for knockout of the insulin receptor (IRKO), which have a mild perturbation of insulin signaling. Male heterozygous IRKO mice aged 8-12 weeks were compared with age- and sex-matched littermates. IRKO mice had fasting blood glucose, insulin, free fatty acid, and triglyceride levels similar to those of wild-type mice. Intraperitoneal glucose and insulin tolerance tests were also similar in the two groups. Insulin levels in response to a glucose load were approximately twofold higher in IRKO compared with wild-type mice (1.08 +/- 0.11 vs. 0.62 +/- 0.13 ng/ml; P = 0.004). Despite this mild metabolic phenotype, IRKO mice had increased systolic blood pressure (124 +/- 4 vs. 110 +/- 3 mmHg; P = 0.01). Basal NO bioactivity, assessed from the increase in tension of phenylephrine preconstricted aortic rings in response to the NO synthase inhibitor N(G)-monomethyl-l-arginine, was reduced in IRKO (61 +/- 14 vs. 152 +/- 30%; P = 0.005). Insulin-mediated NO release in aorta, assessed as the reduction in phenylephrine constrictor response after insulin preincubation, was lost in IRKO mice (5 +/- 8% change vs. 66 +/- 9% reduction in wild-type; P = 0.03). Insulin-stimulated aortic endothelial NO synthase phosphorylation was also significantly blunted in IRKO mice (P < 0.05). These data demonstrate that insulin-stimulated NO responses in the vasculature are exquisitely sensitive to changes in insulin-signaling pathways in contrast to the glucoregulatory actions of insulin. These findings underscore the importance of early intervention in insulin-resistant states, where glucose homeostasis may be normal but substantial abnormalities of the vascular effects of insulin may already be present.

Prolactin, progesterone, and dexamethasone coordinately and adversely regulate glucokinase and cAMP/PDE cascades in MIN6 beta-cells.

Islet cells undergo major changes in structure and function to meet the demand for increased insulin secretion during pregnancy, but the nature of the hormonal interactions and signaling events is incompletely understood. Here, we used the glucose-responsive MIN6 beta-cell line treated with prolactin (PRL), progesterone (PRG), and dexamethasone (DEX, a synthetic glucocorticoid), all elevated during late pregnancy, to study their effects on mechanisms of insulin secretion. DEX alone or combined with PRL and PRG inhibited insulin secretion in response to 16 mM glucose-stimulating concentrations. However, in the basal state (3 mM glucose), the insulin levels in response to DEX treatment were unchanged, and the three hormones together maintained higher insulin release. There were no changes of protein levels of GLUT2 or glucokinase (GK), but PRL or PRG treatment increased GK activity, whereas DEX had an inhibitory effect on GK activity. alpha-Ketoisocaproate (alpha-KIC)-stimulated insulin secretion was also reduced by DEX alone or combined with PRL and PRG, suggesting that DEX may inhibit distal steps in the insulin-exocytotic process. PRL treatment increased the concentration of intracellular cAMP in response to 16 mM glucose, suggesting a role for cAMP in potentiation of insulin secretion, whereas DEX alone or combined with PRL and PRG reduced cAMP levels by increasing phosphodiesterase (PDE) activity. These data provide evidence that PRL and to a lesser extent PRG, which increase in early pregnancy, enhance basal and glucose-stimulated insulin secretion in part by increasing GK activity and amplifying cAMP levels. Glucocorticoid, which increases throughout gestation, counteracts only glucose-stimulated insulin secretion under high glucose concentrations by dominantly inhibiting GK activity and increasing PDE activity to reduce cAMP levels. These adaptations in the beta-cell may play an important role in maintaining the basal hyperinsulinemia of pregnancy while limiting the capacity of PRL and PRG to promote glucose-stimulated insulin secretion during late gestation.

Carbohydrate Metabolism in Gestational Diabetes

In Brief Objective To evaluate whether the coexistence of chronic hypertension and gestational diabetes mellitus (GDM) is characterized by a greater impairment of carbohydrate metabolism than GDM alone. Methods Carbohydrate metabolism of eight women with chronic hypertensive GDM and 15 normotensive women with GDM was evaluated in the third trimester using the oral glucose tolerance test (GTT) and hyperinsulinemic-euglycemic clamp technique. Controls were ten normotensive, glucose-tolerant, pregnant women in the third trimester. Results Insulin sensitivity of women with chronic hypertension and GDM was approximately twofold lower than those with GDM only (1.54 ± 0.35 versus 4.15 ± 0.31, P < .001) and approximately fivefold lower than controls (1.54 ± 0.35 versus 7.65 ± 0.66, P < .001). Women with chronic hypertension and concomitant GDM had higher insulin levels in response to GTT than controls (P < .001 repeated measures analysis of variance). In all subjects, mean arterial pressure (MAP) had a strong negative correlation with maternal insulin sensitivity (r = −0.62, P < .001). Significant correlation was also found between percent of body fat and insulin sensitivity (r = −0.53, P < .002). Those regressions were still significant when adjusted for percent of body fat and MAP. Conclusion Gravidas with chronic hypertension and GDM are more insulin resistant than those with GDM alone. Blood pressure, in a population of pregnant women with normal and abnormal carbohydrate metabolism, is a stronger predictor of insulin resistance than adiposity. Gestational diabetes with concomitant long-term hypertension is characterized by higher insulin resistance than normotensive gestational diabetes.

Carbohydrate metabolism in gestational diabetes: effect of chronic hypertension

Objective: To evaluate whether the coexistence of chronic hypertension and gestational diabetes mellitus (GDM) is characterized by a greater impairment of carbohydrate metabolism than GDM alone. Methods: Carbohydrate metabolism of eight women with chronic hypertensive GDM and 15 normotensive women with GDM was evaluated in the third trimester using the oral glucose tolerance test (GTT) and hyperinsulinemic-euglycemic clamp technique. Controls were ten normotensive, glucose-tolerant, pregnant women in the third trimester. Results: Insulin sensitivity of women with chronic hypertension and GDM was approximately twofold lower than those with GDM only (1.54 ± 0.35 versus 4.15 ± 0.31, P < .001) and approximately fivefold lower than controls (1.54 ± 0.35 versus 7.65 ± 0.66, P < .001). Women with chronic hypertension and concomitant GDM had higher insulin levels in response to GTT than controls ( P < .001 repeated measures analysis of variance). In all subjects, mean arterial pressure (MAP) had a strong negative correlation with maternal insulin sensitivity ( r = −0.62, P < .001). Significant correlation was also found between percent of body fat and insulin sensitivity ( r = −0.53, P < .002). Those regressions were still significant when adjusted for percent of body fat and MAP. Conclusion: Gravidas with chronic hypertension and GDM are more insulin resistant than those with GDM alone. Blood pressure, in a population of pregnant women with normal and abnormal carbohydrate metabolism, is a stronger predictor of insulin resistance than adiposity.

Factors influencing the properties and performance of microcapsules for immunoprotection of pancreatic islets.

There are several approaches of immunoprotection of pancreatic islets for the purpose of successful allo- or xenotransplantation in the absence of immunosuppressive medication. Extravascular approaches are either macroencapsulation (large numbers of islets together in one device) or microencapsulation. The latter approach is to envelop each individual islet in a semipermeable immunoprotective capsule. Quite promising results have been achieved with polylysine-alginate microencapsulated islet grafts in rodents, but clinical application is still restricted to a very small number of cases. Relevant considerations regard the following aspects. The biocompatibility of the microcapsules is influenced by the chemical composition of the materials applied and by mechanical factors related to the production process. With purified instead of crude alginates, the percentage of capsules with fibrotic overgrowth is reduced to approximately ten percent, and the remaining overgrowth is mainly explained by mechanical factors, i.e. inadequate encapsulation of individual islets. Even with purified alginates, however, the duration of encapsulated graft function is limited to a period of six to twenty weeks. Obviously, other factors than bioincompatibility play a role, which factors have to be identified. The limited duration of graft survival cannot be explained by rejection since, in rats, survival times of encapsulated isografts are similar, if not identical, to those of encapsulated allografts. An important factor is probably insufficient nutrition as a consequence of insufficient blood supply of the encapsulated and thus isolated islet. This also influences the functional performance of encapsulated islet grafts. Although normoglycemia can be readily obtained in streptozotocin diabetic rat recipients, glucose tolerance remains severely impaired, as a consequence of an insufficient increase of insulin levels in response to intravenous or oral glucose challenge. Important factors are the characteristics of the capsules applied in view of optimal diffusion kinetics, and the fact that an encapsulated islet graft can only be implanted in the peritoneal cavity because of its volume. Further studies should focus on finding a practically applicable method to reduce the barrier between encapsulated islets and the bloodstream, in order to improve both the functional performance and the survival of encapsulated islet grafts.

Cardiovascular disease and risk factors in adults with hypopituitarism.

In 1992, Cuneo et al. (1992) reviewed, in this journal, the consequences of growth (GH) deficiency during adult life and coined the term ‘Growth hormone deficiency (GHD) syndrome in adults’. Limited information was available then on cardiovascular disease and risk factors in adults with hypopituitarism. More data have been published since on cardiovascular morbidity in symptom-free hypopituitary adults. Several groups have also published results on the effects of GH therapy on cardiac structure and function and on the cardiovascular risk factors. We shall review here the epidemiological and experimental data on cardiovascular morbidity and mortality in adult hypopituitarism. We shall also examine the prevalence of cardiovascular risk factors in this group of patients and their potential causes focusing on the possible role of GH deficiency and the effects of GH replacement.

Impaired pancreatic beta cell function in the fetal GK rat. Impact of diabetic inheritance.

The Goto-Kakisaki (GK) rat is a genetic model of non-insulin-dependent diabetes. At 21.5 d of age we found that GK fetuses had an increased plasma glucose concentration, a decreased plasma insulin level, and a reduced pancreatic beta cell mass. To investigate the beta cell function during fetal life we used a hyperglycemic clamp protocol applied to the mothers, which allowed us to obtain a steady-state hyperglycemia in the corresponding fetuses. At variance, with Wistar (W) fetuses, plasma insulin concentration in GK fetuses did not rise in response to hyperglycemia. In contrast, GK fetal pancreas released insulin in response to glucose in vitro to the same extent as W fetal pancreas. Such a discrepancy between the in vivo and in vitro results suggests that the lack of pancreatic reactivity to glucose as seen in vivo is extrinsic to the fetal GK beta cell. Finally, the importance of gestational hyperglycemia was investigated by performing crosses between GK and W rats. Fetuses issued from crosses between W mother and GK father or GK mother and W father had a beta cell mass close to normal values and were still able to increase their plasma insulin levels in response to hyperglycemia in vivo. Our data suggest that hyperglycemia in utero does not influence the severity of the decrease of the beta cell mass or the lack of the insulin secretory response to glucose in the fetal GK rat. Moreover they indicate that conjunction of GK genes originating from both parents is necessary in order for these defects to be fully expressed.

Impaired glucose tolerance in recipients of an intraperitoneally implanted microencapsulated islet allograft is caused by the slow diffusion of insulin through the peritoneal membrane

I NTRAPERITONEAL transplantation of microencapsulated islets has been reported to restore normoglycemia both in chemically induced and in autoimmune diabetic animal models,‘-5 and recently also in man.6 But a previous report from our laboratory showed that glucose tolerance remains disturbed in spite of normoglycemia, and that there is no increase of plasma insulin levels in response to a physiologic stimulus such as the intake of a meal5 This may be the consequence of several factors such as a gradual decrease of the number of viable and functioning islets after transplantation as a consequence of fibrotic overgrowth of the capsules, or a slow release of insulin in response to a glycemic stimulus as a consequence of overly large capsule diameters.’ The transplantation site as such may be another factor. Previous studies on the kinetics of intraperitoneal insulin absorption report a short delay between the intraperitoneal administration of insulin and rise of plasma insulin levels. *-‘i However, these studies were often performed with insulin bolus injections in unphysiologically high doses which may well be associated with a more rapid absorption of insulin than should be expected with a gradual release of insulin from encapsulated pancreatic islets. Therefore, the present study investigates whether the intraperitoneal implantation site as such interferes with optimal transport kinetics between the islets and the bloodstream.

Glucose and Insulin Response to Carbohydrate Foods in Male Endurance Athletes

The purpose of the study was to determine the effect of three carbohydrate(CHO) foods on plasma glucose and insulin response in trained endurance athletes. Nine, male subjects consumed one of three CHO foods—applesauce(AS), graham crackers(GC) or orange juice(OJ). Test foods were prepared using a formula of 1 gram of CHO per kilogram of body weight. Two days prior to each trial, subjects controlled their dietary intake and exercise output. The composition of the test diet, as a percentage of total calories, was 45% CHO, 15% protein and 40% fat. Ten hours prior to each trial subjects refrained from consuming food and beverages with the exception of water and from engaging in exercise. On the day of the trial, the test food was consumed in six minutes(min), with an additional two min allowed for the consumption of 240ml of water. Subjects then rested quietly for the next 90minutes. Blood samples were collected immediately before the ingestion of the food and at 15,30,45,60,75 and 90min postprandial. Mean glucose concentrations were greatest for OJ at 15min and GC at 30min (113mg/dl). A similar pattern was observed for plasma insulin—47 uU/Lat 30min and 40 uU/L at 15min for GC and OJ respectively. Other than at 15min, there was no significant difference between the glucose means for the three meals. At 15min OJ elicited a significantly greater response than AS. There were no significant differences between the plasma insulin means at baseline or 15min. At 30, 45 and 60minutes, mean plasma insulin response for GC was elevated when compared to AS. Similarly, at 30min GC produced a significantly greater insulin response than OJ. The results suggest that the ingestion of OJ elevates glucose to a greater degree than AS or GC 15min postprandial and that a significant difference exists between mean plasma glucose levels of OJ and AS. At 30min, plasma insulin levels in response to GC ingestion are elevated and are significantly greater than either OJ or AS. This response continues for AS at 45 and 60min but not for OJ. These data add to the growing body of knowledge regarding endurance athletes’ glycemic response to carbohydrate foods.

Glucose and insulin response to carbohydrate foods in male endurance athletes

The purpose of the study was to determine the effect of three carbohydrate(CHO) foods on plasma glucose and insulin response in trained endurance athletes. Nine, male subjects consumed one of three CHO foods—applesauce(AS), graham crackers(GC) or orange juice(OJ). Test foods were prepared using a formula of 1 gram of CHO per kilogram of body weight. Two days prior to each trial, subjects controlled their dietary intake and exercise output. The composition of the test diet, as a percentage of total calories, was 45% CHO, 15% protein and 40% fat. Ten hours prior to each trial subjects refrained from consuming food and beverages with the exception of water and from engaging in exercise. On the day of the trial, the test food was consumed in six minutes(min), with an additional two min allowed for the consumption of 240 ml of water. Subjects then rested quietly for the next 90 minutes. Blood samples were collected immediately before the ingestion of the food and at 15,30,45,60,75 and 90 min postprandial. The highest mean glucose response was for GC at 30 min(120 mg/dl). At 15 min, OJ exhibited the highest mean glucose (113 mg/dl). A similar pattern was observed for plasma insulin—47 uU/L at 30 min and 40 uU/L at 15 min for GC and OJ respectively. Other than at 15 min, there was no significant difference between the glucose means for the three meals. At 15 min OJ elicited a significantly greater response than AS. There were no significant differences between the plasma insulin means at baseline or 15 min. At 30, 45 and 60 minutes, mean plasma insulin response for GC was elevated when compared to AS. Similarly, at 30 min GC produced a significantly greater insulin response than OJ. The results suggest that the ingestion of OJ elevates glucose to a greater degree than AS or GC 15 min postprandial and that a significant difference exists between mean plasma glucose levels of OJ and AS. At 30 min, plasma insulin levels in response to GC ingestion are elevated and are significantly greater than either OJ or AS. This response continues for AS at 45 and 60 min but not for OJ. These data add to the growing body of knowledge regarding endurance athletes' glycemic response to carbohydrate foods.

Evidence against a role of insulin in hypertension in spontaneously hypertensive rats. CS-045 does not lower blood pressure despite improvement of insulin resistance.

Hyperinsulinemia resulting from peripheral insulin resistance has been demonstrated both in spontaneously hypertensive rats (SHR) and in humans with essential hypertension. A new class of antidiabetic drugs, thiazolidinediones, which can improve insulin resistance, may be able to lower not only blood glucose levels but also blood pressure. The present study was therefore designed to clarify the proportion of SHR that are glucose intolerant and to observe the effect on blood pressure of CS-045 (troglitazone) administered at 70 mg/kg per day for 2 weeks to male SHR (n = 13). Among 67 male 8-week-old SHR, 74.6% were glucose intolerant and hyperinsulinemic. Systolic blood pressure did not correlate with plasma glucose or insulin levels before or after glucose loading. Treatment with CS-045 improved insulin resistance, as evidenced by a smaller area under the curve of plasma glucose and insulin levels in response to glucose loading. However, systolic blood pressure was not altered. When the data were reanalyzed according to the presence or absence of glucose intolerance before the treatment, blood pressure in the treated group was the same as in controls despite significant improvement in steady-state plasma glucose levels. These results suggest that hyperinsulinemia and/or insulin resistance may not be involved in the development or maintenance of hypertension in SHR, which is in contrast to models of hypertension such as obese Zucker rats or fructose-fed rats.

The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of polycystic ovarian syndrome.

Hyperandrogenism, insulin resistance, and obesity are common features of polycystic ovarian syndrome (PCOS). This study was designed to investigate the relationship among these factors and how they might contribute to ovulatory dysfunction in PCOS. Adrenal androgen secretion and insulin resistance were quantified in oligomenorrheic women with PCOS and in three groups of eumenorrheic women: weight-matched hirsute women, obese nonhirsute women, and thin nonhirsute women. Adrenal androgen secretion was defined as the androstenedione response to synthetic corticotropin. Insulin resistance was estimated by calculating the area under the curve for serum insulin levels in response to a 75 g oral glucose load. The mean serum androstenedione response (nmol/L) to corticotropin in PCOS (5.6 +/- 1.3) was greater than that in eumenorrheic hirsute women (3.4 +/- 0.5; P < 0.10), obese nonhirsute women (1.8 +/- 0.8; P < 0.05), and lean nonhirsute women (1.9 +/- 0.5; P < 0.05). The serum androstenedione response was not correlated with body mass index (BMI). The area under the curve for serum insulin (mU/L.min/1000) in PCOS (29.1 +/- 5.3) was greater (P < 0.001) than in eumenorrheic hirsute women (9.1 +/- 1.7), obese nonhirsute women (5.8 +/- 1.0), and lean nonhirsute women (4.5 +/- 0.4). The serum insulin response was highly correlated with BMI (P < 0.001) in the three groups of obese women, but women with PCOS became significantly more insulin resistant with increasing BMI (P < 0.02). There was no correlation between adrenal androgen secretion and insulin resistance in any of the groups. We conclude that adrenal hyperandrogenism and insulin resistance are independent predictors of anovulation in hirsute women. These conditions are present in both oligomenorrheic and eumenorrheic hirsute women, but are present to a greater extent in anovulatory women. Obese women with PCOS also differ from eumenorrheic controls by developing a greater degree of insulin resistance as body mass increases.

Effect of some Indian vegetables on the glucose and insulin response in diabetic subjects

The blood glucose levels and the corresponding insulin levels in response to three commonly-used vegetables in southern India in a isocarbohydrate meal were compared to the levels achieved in response to 75g of glucose in non-insulin dependent diabetes mellitus patients. The meals contained 73–79g of available carbohydrate, 10–13.5g of protein, 5g of fat and 0.5–1.3g of crude fibre. The vegetables tested were bittergourd (Momordica charantia; group 1), curry leaves (Murrya koiengii; group 2), and drumstick leaves (Moringa oleifera; group 3). The incremental areas of the standard meal without the vegetable and the test meal with any one of the vegetables were significantly reduced (P ≤ 0.05 for groups 1 and 2, P ≤ 0.01 for group 3) compared to 75g of glucose. The blood glucose responses (as % mean ± s.e.m.) of meals containing bitter gourd, curry leaves or drumstick leaves were 72 ± 10, 60 ± 7 and 56 ± 4, respectively, compared to 75g of glucose, and 88 ± 7, 97 ± 6 and 79 ± 5, respectively, compared to the...

Chronic chloroquine treatment enhances insulin release in rats

The effects of chronic chloroquine treatment on intravenous glucose tolerance, and the plasma insulin response to intravenous glucose were studied in rats. Plasma glucose disappearance constants ( K g) were significantly greater (6.2 ± 0.5 %min −1) than in corresponding controls (3.7 ± 0.4 %min −1, P < 0.001). This improved glucose tolerance was associated with significantly higher plasma immunoreactive insulin levels in response to glucose injection. Islets isolated from rats treated with chloroquine showed significantly enhanced ( P < 0.05) insulin release when incubated with 16.7 mM glucose but not with lower glucose concentrations (3 and 8 mM). Pre-incubation of islets with streptozotocin (0.05–1.5 mg/ml) produced a dose-dependent reduction in glucose-stimulated insulin secretion which was not modified in islets from chloroquine-treated rats. The concentration of chloroquine in the pancreas increased rapidly during administration and reached a value of 20.2 ± 0.7 μg/g (fresh weight) after 20 weeks of treatment. It is concluded that chronic chloroquine treatment results in an improved glucose tolerance associated with an enhanced glucose-induced insulin secretion. Although earlier work showed chloroquine to reduce the severity of diabetes induced subsequently with streptozotocin, the present study shows that such an amelioration was not due to a protective effect against the β-cell cytotoxic action of streptozotocin.

Insulin, glucose, and cortisol levels in bulimia: Effect of treatment

A study is described in which a modified glucose tolerance test was performed in each of five bulimic female patients on two separate occasions. Two of the patients were poorly controlled outpatients and three were inpatients in a strict hospital program of nutritional rehabilitation and psychotherapy. Plasma glucose, insulin, and cortisol levels, in response to a glucose load and following 3 days of normal nutrition, were compared with those documented following engagement in various bulimic behaviors during the preceding 24 hours (i.e., fasting, binging, and vomiting.). In all five patients, following bulimic behaviors, peak insulin levels in response to a glucose load and the area under the curve of insulin secretion was increased whereas cortisol levels were lower, even in the one patient who was hypercortisolemic. However, the insulin peaks were less in evidence in the treated patients than in those who continued to engage in bulimic behavior, and there was also less evidence of cortisol suppression in the treated patients. Furthermore, insulin secretion as measured by Tmax occurred more rapidly after engagement in bulimic behavior and was delayed in treated patients following normal nutrition. It is postulated that insulin potentiation and suppression of stress hormones as reflected by serum cortisol are important self-perpetuating mechanisms in bulimia and that these are related to the occurrence of intermittent starvation and its relief through binge eating. Treatment reduces this effect by reestablishing regular nutrition.

The [formula omitted] effect of 1α,25-dihydroxyvitamin D 3 on insulin production by neonatal rat islets

The in vitro effect of 1α,25-dihydroxyvitamin D 3 on the function of beta cells of the endocrine pancreas was investigated. Neonatal islets maintained in serum-free medium, or medium supplemented with 0.5% fetal bovine serum achieved a 2.5-fold increase in medium insulin levels in response to 10 −8M 1α,25-dihydroxyvitamin D 3 (P<0.001). The effect of 1,25-dihydroxyvitamin D 3 required at least 96 h treatment to become evident and was similar at medium glucose concentrations of 10 and 20 mM. Cell-associated insulin was increased in 1α,25-dihydroxyvitamin D 3-treated cultures maintained in 0.5% serum. These data suggest that 1α,25-dihydroxyvitamin D 3 may have a direct effect in the beta cell.